This invention relates to the receptor CMRF-35-H9 which inter alia binds immunoglobulin M(IgM)
It is well known that the human immune response is stimulated by foreign antigen (Ag). Antigen presenting cells, such as the dendritic cells perform important immunoregulatory functions by presenting antigens in the form of peptides bound to cell-surface major histocompatibility complex (MHC) molecules to T cells. This initiates a T lymphocyte response which is followed by a humoral or antibody (B lymphocyte derived) immune response. Humoral responses include a primary response with antibodies of the IgM isotype followed by a secondary response with immunoglobulin of the IgG, IgA and IgE isotype. The soluble immunoglobulin interact with Ag in the tissues (opsonisation) and bind, via their functional components (Fc) to receptors (Fc receptors) on different types of white blood cells.
Given that IgM is the primary antibody produced, the identification and characterisation of cellular IgM receptors and binding proteins has important implications in manipulating immune response in prophylaxis and therapy, particularly in humans.
The applicant has now identified a receptor on human dendritic and other cells which binds IgM. It is broadly to this receptor, which the applicants have called CMRF-35-H9, that the present invention is directed.
The present invention has a number of aspects. In a first aspect, the invention provides human CMRF-35-H9 which has the amino acid sequence set out in FIG. 2 (SEQ ID NO. 1), or a functionally equivalent variant thereof.
In a further aspect, the invention provides a peptide encoding domain of receptor CMRF-35-H9, which is comprised of amino acids 14 to 177 of the amino acid sequence of FIG. 2 (SEQ ID NO. 3), or a functionally equivalent variant thereof.
In a still further aspect, the invention provides a polynucleotide encoding receptor CMRF-35-H9 and/or its extracellular domain as defined above. This polynucleotide molecule is preferably DNA, more preferably cDNA, but can also be RNA.
In one embodiment, the DNA molecule coding for receptor CMRF-35-H9 comprises the nucleotide sequence set out in FIG. 2 (SEQ ID NO. 4), or a sequence which is a functionally equivalent variant thereof.
In a further embodiment, the present invention provides a DNA molecule coding for a peptide encoding the extracellular domain of human CMRF-35-H9 which comprises nucleotides 120 to 611 of FIG. 2 (SEQ ID NO. 6).
In yet a further aspect, the invention provides a vector including a polynucleotide as defined above.
In still a further aspect, the invention provides a method of producing receptor CMRF-35-H9 or the extracellular domain thereof comprising the steps of:
(a) culturing a suitable host cell which has been transformed or transfected with a vector as defined above to express the encoded receptor CMRF-35-H9 or extracellular domain; and
(b) recovering the expressed receptor CMRF-35H9 or extracellular domain.
In a still further aspect, the present invention provides for the use of receptor CMRF-35-H9 or extracellular domain thereof in the preparation of a medicament suitable for use in methods of therapy or prophylaxis.
Pharmaceutical compositions comprising receptor CMRF-35-H9 or the extracellular domain thereof also form part of the present invention.
Other aspects of the invention will be apparent from the description which follows and from the attached claims.